Proteolysis is of paramount importance to biological regulation, and its significance is magnified because it is irreversible. Proteolysis regulates the four fundamental aspects of cell behavior; division, death, differentiation and motility. Proteolytic pathways are key to the pathology of virtually every type of human disease including, infection, inflammation, thrombosis, cancer, emphysema, Alzheimer's, etc. The importance and impact of understanding proteolysis "in total" will be immense. Achieving this ultimate goal will be a considerable challenge, and one that will require an ambitious and coordinated effort. Here we propose to form the Center on Proteolytic Pathways (CPP), a National Resource for the study of proteases, their inhibitors, their products, and upstream and downstream regulatory pathways. The strategic goal of the CPP is to develop The Protease Pathway Interrogation Platform (PPIP) technology. This platform technology will be comprised of four foundation technologies; (1) Activity-based Protease Profiling, (2) Protease Activity Imaging Technology, (3) Product Terminal Isotope Coding, and (4) the in silico environment called Protease Map. A key and unique feature of this technology platform is its focus squarely on measuring activity, as opposed to just abundance. The CPP will contain a Training component to ensure that a new cadre of scientists is trained to tackle protease biology with the most modem of techniques and most cutting edge technology. An Outreach component is planned to ensure that the CPP achieves high visibility, and ultimately numerous connections, with the scientific research community. [unreadable] [unreadable] [unreadable]